Journal article
Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer's disease
Translational Psychiatry, Vol.5, e494
2015
Abstract
There is an urgent need for the identification of Alzheimer’s disease (AD) biomarkers. Studies have now suggested the promising use of associations with blood metabolites as functional intermediate phenotypes in biomedical and pharmaceutical research. The aim of this study was to use lipidomics to identify a battery of plasma metabolite molecules that could predict AD patients from controls. We performed a comprehensive untargeted lipidomic analysis, using ultra-performance liquid chromatography/mass spectrometry on plasma samples from 35 AD patients, 40 elderly controls and 48 individuals with mild cognitive impairment (MCI) and used multivariate analysis methods to identify metabolites associated with AD status. A combination of 10 metabolites could discriminate AD patients from controls with 79.2% accuracy (81.8% sensitivity, 76.9% specificity and an area under curve of 0.792) in a novel test set. Six of the metabolites were identified as long chain cholesteryl esters (ChEs) and were reduced in AD (ChE 32:0, odds ratio (OR)=0.237, 95% confidence interval (CI)=0.10–0.48, P=4.19E−04; ChE 34:0, OR=0.152, 95% CI=0.05–0.37, P=2.90E−04; ChE 34:6, OR=0.126, 95% CI=0.03–0.35, P=5.40E−04; ChE 32:4, OR=0.056, 95% CI=0.01–0.24, P=6.56E−04 and ChE 33:6, OR=0.205, 95% CI=0.06–0.50, P=2.21E−03, per (log2) metabolite unit). The levels of these metabolites followed the trend control>MCI>AD. We, additionally, found no association between cholesterol, the precursor of ChE and AD. This study identified new ChE molecules, involved in cholesterol metabolism, implicated in AD, which may help identify new therapeutic targets; although, these findings need to be replicated in larger well-phenotyped cohorts.
Details
- Title
- Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer's disease
- Authors/Creators
- P. Proitsi (Author/Creator) - King's College LondonM. Kim (Author/Creator) - King's College LondonL. Whiley (Author/Creator) - King's College LondonM. Pritchard (Author/Creator) - King's College LondonR. Leung (Author/Creator) - King's College LondonH. Soininen (Author/Creator) - University of Eastern FinlandI. Kloszewska (Author/Creator) - Medical University of LodzP. Mecocci (Author/Creator) - University of PerugiaM. Tsolaki (Author/Creator) - Aristotle University of ThessalonikiB. Vellas (Author/Creator) - InsermP. Sham (Author/Creator) - University of Hong KongS. Lovestone (Author/Creator) - Warneford HospitalJ.F. Powell (Author/Creator) - King's College LondonR.J.B. Dobson (Author/Creator)C. Legido-Quigley (Author/Creator) - King's College London
- Publication Details
- Translational Psychiatry, Vol.5, e494
- Publisher
- Macmillan Publishers Limited
- Identifiers
- 991005544743407891
- Copyright
- © 2015 Springer Nature Limited
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.211 Mass Spectrometry
- 2.211.990 Metabolomics
- Web Of Science research areas
- Psychiatry
- ESI research areas
- Psychiatry/Psychology